Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2006-9-28
pubmed:abstractText
An inverse relationship exists between the expression of 15-lipoxygenase-2 (15-LOX-2) and peroxisome proliferator-activated receptor gamma (PPARgamma) in normal prostate epithelial cells (PrECs) compared with their expression in prostate carcinoma cells (PC-3). The reason for this difference, however, is unknown. We hypothesized that this inverse expression partly involves the 15-LOX-2 promoter and 15-S-hydroxyeicosatetraenoic acid (15-(S)-HETE), a product of 15-LOX-2 that binds to PPARgamma. We identified an active steroid nuclear receptor half-site present in the 15-LOX-2 promoter fragment F-5 (-618/+177) that can interact with PPARgamma. After forced expression of wild-type PPARgamma, 15-(S)-HETE (1 microM) decreased F-5 reporter activity in PrECs whereas forced expression of 15-LOX-2 resulted in 15-(S)-HETE production which enhanced F-5 activity in PC-3. In contrast, the expression of dominant-negative PPARgamma reversed the transcriptional activation of F-5 by enhancing it 202-fold in PrEC or suppressing it in PC-3; the effect in PC-3 was positively increased 150-fold in the presence of 15-(S)-HETE (1 microM). Peroxisome proliferator-activated receptor gamma interacted with 15-LOX-2 promoter sequences in pulldown experiments using biotinylated 15-LOX-2 (-560/-596 bp) oligonucleotides. In gelshift analyses PPARgamma and orphan receptor RORalpha were shown to interact with the F-5 fragment in PC-3 cells. These data suggest that crosstalk mechanisms exist between the 15-LOX-2 gene and PPARgamma to counterbalance expression and help explain the inverse relationship of these genes in normal versus cancer cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6015-25
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16682954-5' Untranslated Regions, pubmed-meshheading:16682954-Arachidonate 15-Lipoxygenase, pubmed-meshheading:16682954-Cell Line, pubmed-meshheading:16682954-Cell Line, Tumor, pubmed-meshheading:16682954-Chromosomes, Human, Pair 17, pubmed-meshheading:16682954-Cloning, Molecular, pubmed-meshheading:16682954-Down-Regulation, pubmed-meshheading:16682954-Enhancer Elements, Genetic, pubmed-meshheading:16682954-Feedback, Physiological, pubmed-meshheading:16682954-Humans, pubmed-meshheading:16682954-Hydroxyeicosatetraenoic Acids, pubmed-meshheading:16682954-Lipoxygenase Inhibitors, pubmed-meshheading:16682954-Male, pubmed-meshheading:16682954-PPAR gamma, pubmed-meshheading:16682954-Promoter Regions, Genetic, pubmed-meshheading:16682954-Prostate, pubmed-meshheading:16682954-Prostatic Neoplasms, pubmed-meshheading:16682954-Receptor Cross-Talk, pubmed-meshheading:16682954-Up-Regulation
pubmed:year
2006
pubmed:articleTitle
15-Lipoxygenase-2 gene regulation by its product 15-(S)-hydroxyeicosatetraenoic acid through a negative feedback mechanism that involves peroxisome proliferator-activated receptor gamma.
pubmed:affiliation
Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural